Substance abuse rates among Native American Indian youth are higher than among all other youth. Native American Indian youth are considered to be at risk for continuing life-threatening problems such as accidents, chronic liver disease, homicide, and suicide as a result of substance abuse. Native American Indian early adolescents have higher risk for substance use as they transition along the periods of adolescence than non-Native American Indian early adolescents. Among Native American Indian youth, substance use has been attributed to the large amount of social interaction and influence from older adolescent youth with their younger peers. Cherokees are the second-largest tribe in the U.S., accounting for a large percentage of alcohol and drug abuse among Native American Indians. In Oklahoma, the home of Cherokee Nation where the study will occur, it is estimated that 20,000 adolescents have alcohol and drug abuse issues. During the last several decades, the field of substance use research among Native American Indian youth has been dominated by survey approaches that fail to answer important questions about how the use of alcohol and drugs is integrated into the lives of Native American Indians. The values that serve as protective factors for Native American Indians need to be integrated, measured and thoughtfully examined for potential to influence substance use prevention. At this time, there is no research addressing the use of culturally competent substance use prevention for Native American Indian early adolescents. The overall objective of the Testing a Substance Abuse Prevention for Cherokee Early Adolescents study is to examine the feasibility (Specific Aim #1) of using an innovative culturally appropriate school- based substance use prevention [Cherokee Talking Circle (CTC)] for Cherokee 6th graders as they transition to middle school, a period of high vulnerability. The impact of the CTC on substance use involvement (measured by the GAIN-Q) and Cherokee self-reliance (measured by the Cherokee Self-Reliance Questionnaire) will be assessed (Specific Aim #2) using a two- condition quasi-experimental design, comparing the CTC to standard substance use education. Data from this quasi-experimental study will be used to estimate the prevention effect size (Specific Aim #3), a critical step necessary before proposing a cross-tribal, cross-age, multi-site study examining substance use prevention in Native American youth. The PI is a Native American Indian (Cherokee) tribal member who has done more than a decade of research developing and testing the CTC and the Cherokee Self-Reliance Questionnaire. PUBLIC HEALTH RELEVANCE: Substance abuse prevention studies among Native American Indian early adolescents are non- existent, despite evidence that substance abuse is an increasing problem in this population. This study will examine the feasibility of using an innovative culturally appropriate school-based substance use prevention for Cherokee 6th graders as they transition to middle school, a period of high vulnerability.